Glycolysis is accelerated in oxygen deficient hearts that receive normal rates of coronary flow, but this source of ATP is inhibited when coronary flow is reduced. In ischemic hearts, oxidation of fatty acids is reduced and more fatty acids are converted to tissue lipids. The present study proposed to study the biochemical mechanisms that regulate glycolysis and fatty acid metabolism in oxygen deficient rat hearts. Hearts will be isolated and perfused under hypoxic and ischemic conditions at various rates of oxygen delivery and coronary flow. The rates of glycolysis and triglyceride synthesis and the tissue levels of metabolites within these pathways will be determined. The mechanisms that alter rates of these pathways will be studied by determining the rate-limiting steps in control, hypoxic and ischemic hearts and the factors that control flux through these steps. Determining the control mechanisms in these pathways will facilitate development of a metabolic and pharmacological intervention designed to improve energy metabolism in various forms of cardiac diseases. BIBLIOGRAPHIC REFERENCES: J. R. Neely, J. T. Whitmer and M. J. Rovetto. Effect of coronary blood flow on glycolytic flux and intracellular pH in isolated rat hearts. Circ. Res. 37: 733-741, 1975.